Preclinical toxicologic evaluation of ICRF-187 in dogs

Single- and multiple-treatment schedule in dogs were used to evaluate the toxicity of ICRF-187. The major target organs were the bone marrow, lymphoid tissue, gastrointestinal tract, liver, and kidney. Liver, kidney, and intestinal toxic effects were most severe at lethal doses. Toxic effects on the kidney and intestinal tract were reduced or absent at lower doses. Hepatotoxicity was most severe after single doses and was only slowly reversible at high doses. Repeated dosage regimens had the greatest effect on circulating blood cells, and anemia and neutropenia were most prominent after three series of five daily doses with rest periods between series. ICRF-187 was more toxic to dogs in terms of total dose received when administered in five daily doses than in single doses. A rest period between series of five daily doses allowed a larger total dose to be administered.